Biomedical subjects
Publications and source records attributed to W Müller.
61 procedures using an alternative vascular access for PTA are reported. Puntures of mid and distal femoral arteries and popliteal arteries in antegrade as well as retrograde direction have been proven effective and sufficiently safe, when unfavourable anatomic situations did not allow the performance of a standard procedure. 14 cases necessitated puncture of and access via crural arteries.
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The generalized tendomyopathy (fibromyalgia) is characterized by the characteristic picture of multilocular pain symptoms, severe pressure-type pain in the tendon insertions and muscles, vitality deficiency, sleep disturbance and other vegetative disorders as well as functional complaints and is often also characterized by an altered psychological condition. Nevertheless, the disease is often not recognized, resulting in extensive superfluous diagnostic procedures and sometimes invasive and useless therapeutic measures. The disorder develops on average in the 37th year of life and initially affects, mostly monolocular, the cervical and lumbar region. The further course of the disease is progressive or recurrent and extends over years, often over decades. The patients' quality of life is markedly impaired and in many cases they are no longer able to carry out their occupational and household work. The socioeconomic significance of the generalized tendomyopathy probably exceeds that of chronic polyarthritis. One problem is the still poor therapeutic possibilities and also the assessment of the treatment. It is, therefore, of great importance to follow the course of the disease and the pain course via hand measurement methods, so as to enable the evaluation of new, but also known therapies. Measuring instruments, which record the intensity and the topography of the pain, such as dolorimetry and the pain score, will be presented and discussed. One of the newest possibilities is the computerized recording of the current symptoms, which is made by the patient himself by means of an electronic pain diary.
Pseudomonas aeruginosa was isolated from sinks of washing basins, showers, toilets and bathtubs, from the personnel and patients of a mixed infectious disease ward in a German children's hospital during a prospective 4-week epidemiological study. 81% of all sinks were contaminated with P. aeruginosa strains. Upon entering the hospital, all personnel hand cultures were P. aeruginosa-negative. However, during duty, 42.5% of the personnel members carried different P. aeruginosa strains on their hands. Detection of P. aeruginosa strains in sinks preceding the isolation of identical genotypes from personnel hands suggested a transmission route from sinks to hands. Opening of water taps generated aerosols containing P. aeruginosa sink organisms which contaminated hands during hand washing. Survival times of various P. aeruginosa strains in aerosols was dependent on strain characteristics, light and humidity, and t 1/2 differed between 3-76 min. Heating of washing basin sinks to 70 degrees C with a new, safe and inexpensive device inhibited bacterial growth in sinks, generation of P. aeruginosa aerosols, and resulted in hand cultures negative for P. aeruginosa after washing.
Magnesium was found to accumulate in cross bands of myocytes due to myofibrillar degeneration in the context of myocardial lesions and was also detected from contraction bands in injured fibres of duck feather muscles. Relevant findings were based on histochemical detection of magnesium with quinalizarin, magnesone, and titan-yellow. Amassed degenerated myofibrils and injured mitochondria were supposed to make for the substrate of magnesium. Elective staining of cross bands by Luxol Fast Blue MBS was assumed to be attributable to bondability to divalent cations.
The generalised tendomyopathy (fibromyalgia) is one of the most frequent rheumatological diseases and has a prevalence of approximately 1%. Multilocular conditions of pain of the back, the extremities and the face with increased tenderness on pressure on defined insertions and courses of the tendons clinically stand to the fore. Functional disturbances, vegetative symptoms and psychopathologic changes are frequently connected with this. Laboratory investigations are normal. The diagnosis results from the combination of multilocular conditions of pain - combined with the defined tenderness on pressure mentioned and as additional symptoms functional disturbances, vegetative symptoms and psychopathological changes. In the genesis of the disease probably reflex mechanisms on the part of the spinal column, partly also on the peripheral joints primarily play a role. Probably the generalisation is evoked above all by psychosocial factors which possibly cause the various symptoms by a continuous impulse on the reticular formation.
In the treatment of inflammatory rheumatic diseases with chronic course, operative and respectively arthroscopic synovectomy on the one hand and synoviorthesis on the other hand come into question. Synoviorthesis by corticosteroids has a very large indication if the corresponding measures of precaution are heeded. Chemical synoviorthesis, mainly by osmium tetroxide, is applied above all in exudative inflammatory diseases, whereas radiosynoviorthesis with the nuclides used at present is mainly applied in proliferative diseases; as a rule, synovectomy should be preferred in young patients. Likewise, synovectomy is the method of choice, respectively, in tenosynovitis and if reconstructive measures at the joint are necessary.
141 Haemophilus (H.) parasuis and 8 H. parasuis-like strains from different farms were serotyped according to Morozumi and Nicolet (1986 b) as well as to Bakos et al. (1952). It was possible to classify 72.8% of the investigated strains. 7 out of 12 serotypes have been described for the first time. The high specificity in the agar gel precipitation test was not reproducible in the more sensitive dot-blot procedure. The dot-blot results point to a participation of non-immunogenic polysaccharides in the detection reaction. The serotypes SV 1, SV 5, SV Jena 6 and SV Jena 10 proved to be highly virulent in SPF pigs, SV 2 and SV 4 were of medium virulence. The other serotypes were found to be nonvirulent. Unencapsulated strains and isolates of serotype SV 5 prevailed in animals with Glasser's disease. 23 H. parasuis and 3 H. parasuis-like strains were examined in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). On the basis of protein profiles of whole-cell lysates, 23 of them could be assigned to 5 groups. Apart from the highly virulent strains of serovar 1, which belonged to PAGE type III, all other highly virulent strains of the serovars SV 5, SV Jena 6 and SV Jena 10 were grouped into PAGE type I. No correlation could be found between PAGE type on the one hand and virulence or origin of isolates on the other hand.
Sixty patients with metastatic renal cell carcinoma were entered into an ongoing randomized phase II study with lonidamine, 350 mg/m2 orally daily (arm A) and high dose tamoxifen, 150 mg/m2 orally daily for 6 months, afterwards 50 mg/m2 (arm B), until tumor progression. All patients had measurable disease and documented tumor progression prior to treatment. There were 1 complete and 1 partial remission among 19 evaluable patients in arm A (10.5%) and 2 complete and 1 partial remission among 25 evaluable patients (12%) in arm B. Objective responses were observed in pulmonary, nodal, and cutaneous metastases. In addition, in 63% and 64% tumor progression could be stopped in arm A and B, respectively. Median response duration was 100 days (range, 20-361) in arm A and 150 days (range, 28-355) in arm B. One year survival rate was 37.5% with lonidamine and 35% with tamoxifen. In arm A patients with tumor progression within 12 weeks after diagnosis of metastatic disease survived significantly shorter than patients with a longer interval (P less than 0.05). Nephrectomy or number and localization of metastatic sites failed to significantly influence probability of remission or survival. Toxicity was mostly mild to moderate. Four patients in the lonidamine arm had to discontinue treatment because of intolerable myalgias, which were immediately reversible. These data suggest that lonidamine and high-dose tamoxifen are moderately effective in widespread renal cell carcinoma where treatment intention is palliative.
An instrumental device is described which allows steady-state kinetic measurements of photophosphorylation at a desired proton gradient which can be maintained throughout the course of the experiment ('delta pH clamp'). This is achieved by electronic regulation of light intensity using the calibrated 9-aminoacridine fluorescence signal as sensor of the gradient. The instrument is suitable for determination of kinetic parameters of the proton-translocating ATPase in isolated envelope-free chloroplasts under defined conditions. At clamped delta pH, phosphorylation as a function of substrate concentration shows Michaelis-Menten kinetics. The true Michaelis constants and the dissociation constants for phosphate and ADP are reported. The Michaelis constants are not affected by the magnitude of the proton gradient in the investigated range. The significance of these results is discussed.
A fully automated high-performance liquid chromatographic method is described for the determination of the new H+/K+ ATPase inhibitor BY 1023/SK&F 96,022 and its major metabolite occurring in dog serum. The method uses direct sample injection of up to 200 microliters and a pre-column switching technique. In order to optimize the recovery, pre-column conditions were varied systematically with respect to the pH of the pre-column eluent, its buffering capacity and content of acetonitrile. Optimization resulted in near 100% recovery for both compounds, thus allowing the use of external standardization. The linearity range, precision and detection limits were determined and the method shown to be applicable to both serum and plasma. The method was applied to define the pharmacokinetics in dogs and humans.
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An artificial immune complex consisting of IgG covalently bound to polyacrylic acid (PAIGP) was prepared and investigated for its influence on a number of immunological reactions attributed to natural immune complexes. PAIGP consumed complement in a fast reaction. Complement consumption was complete after 10 min of incubation of guinea-pig serum with PAIGP. The concentration of PAIGP for 50% consumption was 2.3 micrograms/ml. PAIGP induced a chemiluminescence response in human peripheral polymorphonuclear leukocytes. This response was elicited in the absence and presence of serum and in whole blood. The response was maximal for leukocytes in the absence of serum and rather low in whole blood. The induction of chemiluminescence by PAIGP was inhibited by monoclonal antibodies to one of the Fc receptors of leukocytes (anti-Leu 11B), while unrelated antibodies had no influence on the chemiluminescence induced by PAIGP. PAIGP also stimulated the production of superoxide anion by polymorphonuclear leukocytes. The efficacy of PAIGP in stimulation of superoxide production was comparable to phorbol myristate acetate (PMA) and opsonized zymosan. PAIGP induced the discharge of elastase, a constituent of the azurophile granules of PMN leukocytes. Here, PAIGP was a rather weak stimulus compared to opsonized zymosan. PMA proved unable to induce elastase release. Thus, PAIGP induced a number of biological reactions usually brought about by naturally occurring antigen antibody complexes.
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Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes. We treated five patients with SCN with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 42 days and subsequently, between 1 and 3 months later, with rhG-CSF for 142 days. The objective was to evaluate the safety and ability of these factors to elicit a neutrophil response. rhGM-CSF was administered at a dose of 3 to 30 micrograms/kg/d (30 to 60 minutes, intravenously). In all patients, a specific, dose-dependent increase in the absolute granulocyte counts was observed. However, in four patients this increase was due to an increase in eosinophils, and in only one patient it was due to an increase in the absolute neutrophil counts (ANC). Subsequently, all patients received rhG-CSF at a dose of 3 to 15 micrograms/kg/d subcutaneously. In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment. In one patient, the increase in ANC was associated with an improvement of a severe pneumonitis caused by Peptostreptococcus and resistant to antibiotic treatment. No severe bacterial infections occurred in any of the patients during CSF treatment. All patients tolerated rhGM-CSF and rhG-CSF treatment without severe side effects. These results demonstrate the beneficial effect of rhG-CSF in SCN patients.
Incubation of the human monoblastoid tumor cell line U937 with 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days was associated with marked morphological and functional changes including adherence of the cells and cessation of proliferation. While growth arrest and the viability of the cells were not influenced, the TPA-induced adherence of U937 cells could be totally blocked by incubation with tunicamycin, suggesting an involvement of N-linked carbohydrates in these cell attachment processes. The isolation and characterization of endogenous lectins with specificities for lactose, L-fucose, and D-mannose from U937 controls and TPA-differentiated U937 cells demonstrated marked differences in either the pattern and the distribution of these sugar-specific carbohydrate-binding proteins. Our results indicate that alterations in cell-surface carbohydrates are of central importance for the attachment of the differentiating U937 tumor cells.
A flexible, fast and simple magnetic cell sorting system for separation of large numbers of cells according to specific cell surface markers was developed and tested. Cells stained sequentially with biotinylated antibodies, fluorochrome-conjugated avidin, and superparamagnetic biotinylated-microparticles (about 100 nm diameter) are separated on high gradient magnetic (HGM) columns. Unlabelled cells pass through the column, while labelled cells are retained. The retained cells can be easily eluted. More than 10(9) cells can be processed in about 15 min. Enrichment rates of more than 100-fold and depletion rates of several 1,000-fold can be achieved. The simultaneous tagging of cells with fluorochromes and very small, invisible magnetic beads makes this system an ideal complement to flow cytometry. Light scatter and fluorescent parameters of the cells are not changed by the bound particles. Magnetically separated cells can be analysed by fluorescence microscopy or flow cytometry or sorted by fluorescence-activated cell sorting without further treatment. Magnetic tagging and separation does not affect cell viability and proliferation.